The patented Hypoxyprobe TM system for measuring tissue hypoxia has been licensed for use in experimental animals. In addition, an FDA IND is available for the clinical application of Hypoxyprobe ru- 1 and the marker is being used in clinics in the US, Canada and Europe. Over 500 patients have received the marker and exciting mechanistic and treatment planning results are being reported. For example, HypoxyproberU-1 (pimonidazole hydrochloride) has predicted local radiation response and has demonstrated the efficacy of an intervention designed to decrease tumor hypoxia during radiation therapy. These successes indicate the value of the Hypoxyprobe TM system. The present proposal is designed to make the marker system even more attractive to patients and clinicians as a routine clinical procedure. The Hypoxyprobe TM procedure is "low tech" and readily incorporated into routine clinical practice. It is well tolerated by patients with no adverse events attributable to the marker. However, intravenous infusion of HypoxyproberM-1 is used and, while most patients tolerate this, we believe that oral administration would improve patient comfort, maximize compliance and set the stage for Hypoxyprobe TM commercialization for companion animal and human use. In the present Phase I application, the safety and efficacy of oral administration of two Hypoxyprobe TM hypoxia markers, HypoxyproberM-1 and HypoxyproberM-F6, will be examined in canine patients in the clinical setting of a Veterinary Hospital. Two experiments are planned. In one, the equivalency of oral and intravenous infusion of the markers in detecting tumor hypoxia will be tested. In the second experiment, the equivalency of the two markers when both are administered orally will be tested. The test will be in the context of a sham irradiation experiment that will set the stage for a detailed examination of the effect of irradiation on tumor hypoxia in a projected Phase II study. Pharmacokinetic studies for the two markers will be carried out in both experiments.